This application relates to a novel lyophilized product and to a process for its preparation. More specifically, it relates to a lyophilized form of a substance having at least one biologically active component.
Biologically active products, including: pharmaceuticals such as vitamins, hormones, tranquilizers and antibiotics; proteins such as enzymes and gelatins; and control products such as plasma or serum are in wide spread use. Despite this fact, there are still many problems with the way in which they are produced and the form in which they are provided. For example, since they are biologically active, they should be provided in a form which will preserve their biological activity for a reasonable time. One method of accomplishing this is to freeze the substance and retain it in its frozen state. This, however, entails the extra handling and equipment necessary to keep the substance frozen at all times.
Alternatively, quantities of the substance have been frozen in bulk and subsequently lyophilized. The product no longer has to be maintained below freezing, but the slow freezing that takes place during bulk freezing creates other problems. For one thing, slow freezing promotes the development of concentration gradients. When blood serum or plasma is frozen slowly, for example, the cholesterol and triglyceride globules within the serum or plasma are forced to coalesce. These globules, upon dissolution of the lyophilized product in an aqueous solvent, apparently do not redisperse but remain coalesced. The result is a non-uniform product.
Another problem that slow freezing produces is degradation of the various biological constituents. Freezing of enzyme solutions, for example, generally appears to have a degradative effect upon the enzymes. The slow freezing that takes place when bulk freezing is used and the concentration gradients that build up in such products merely increase this degradation. One effort to counteract the enzyme degradation resulting from the slow freezing of a plasma, for example, has been to entirely remove the enzyme and other constituents from the plasma and to weigh in predetermined quantities of these substances to achieve constant level after the product is frozen and dried. The weight of an enzyme, however, does not truly represent the amount of material that should be added. As enzymes are subject to degradation, the true measure of enzyme concentration is activity, for which weight is not an accurate substitution.
Finally, the reconstitution of lyophilized substances by dissolution in water meets with difficulties when the substance is frozen in bulk form. Such reconstitution often requires upwards of 20 to 30 minutes and often results in a lack of clarity. This is a particularly bothersome problem with control products, such as serum or plasma, when subsequent photometric analysis is performed on them. Furthermore, when the products are frozen in bulk form, they are difficult to dispense in any other form but the reconstituted form.